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Oral acetaminophen as an adjunct to continuous epidural infusion and patient-controlled epidural analgesia in laboring parturients: a randomized controlled trial

A Letter to the Editor to this article was published on 11 August 2021



Intravenous acetaminophen is safe and effective as an adjunct to labor analgesia with combined spinal–epidural (CSE) analgesia and patient-controlled epidural analgesia (PCEA). Oral acetaminophen is a much cheaper and safe option but has not been studied as an adjunct to labor analgesia till date. The aim of the present study is to evaluate the effect of oral acetaminophen as an adjunct in patients receiving local anesthetic-opioid combination using CSE analgesia.


In this ethically approved randomized double-blind placebo-controlled trial, 60 consenting parturients were randomly allocated to two groups of 30 each: acetaminophen (who received oral acetaminophen 1 g) or placebo, 45 min before the procedure. CSE was administered as per hospital protocol. All the patients received continuous epidural infusion (CEI) of levobupivacaine 0.1% and fentanyl 2 mcg/mL at 5 ml/h and PCEA boluses of 5 mL of the same drug with a lockout interval of 15 min if needed.

The primary outcome was hourly mean consumption of levobupivacaine and fentanyl mixture (mL/h). Secondary outcomes included pain score, sensory and motor block, hemodynamic parameters of mother, duration of the second stage of labor, mode of delivery, maternal satisfaction, Apgar scores, fetal heart rate, and adverse effects.


The mean drug consumption per hour was significantly less in the acetaminophen group than in the placebo group (7.66 mL/h, SD 2.01 vs. 9.01 mL/h, SD 2.83; p = 0.04). The requirement for bolus was also significantly less in the acetaminophen group than in the placebo group (median 2.5, IQR 3 vs. median 3.5, IQR 2; p = 0.04).


The use of 1 g of oral acetaminophen could be a cheap, safe, and effective adjunct to CEI plus PCEA in labor analgesia.

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Fig. 1


  1. 1.

    Gupta K, Mitra S, Kazal S, Saroa R, Ahuja V, Goel PIV. paracetamol as an adjunct to patient-controlled epidural analgesia with levobupivacaine and fentanyl in labour: a randomized controlled study. Br J Anaesth. 2016;117:617–22.

    CAS  Article  Google Scholar 

  2. 2.

    ACOG Committee Opinion #295: pain relief during labor. Obstet Gynecol 2004;104(1):213.

  3. 3.

    Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database Syst Rev. 2018 May 21;5(5):CD000331.

  4. 4.

    Koepke EJ, Manning EL, Miller TE, Ganesh A, Williams DGA, Manning MW. The rising tide of opioid use and abuse: the role of the anesthesiologist. Perioper Med. 2018;7:16. (E-Collection 2018).

    Article  Google Scholar 

  5. 5.

    Sullivan GO. Epidural analgesia for labor. Eur J Pain. 2009;3:65–70.

    Article  Google Scholar 

  6. 6.

    Lim Y, Sia AT, Ocampo CE. Comparison of intrathecal levo-bupivacaine with and without fentanyl in combined spinal epidural for labor analgesia. Med SciMonit. 2004;10:PI87-91.

    CAS  Google Scholar 

  7. 7.

    Robinson AP, Lyons GR, Wilson RC, Gorton HJ, Columb MO. Levobupivacaine for epidural analgesia in labor: the sparing effect of epidural fentanyl. AnesthAnalg. 2001;92:410–4.

    CAS  Google Scholar 

  8. 8.

    Simkin P, Dickersin K. Control of pain in labor. In: M Enkin, M Keirse, J Neilson, C Crowther, L Duley, E Hodnett, et al., eds. A Guide to Effective Care in Pregnancy and Childbirth, 3rd Ed. New York: Oxford University Press, 2000; 313–31.

  9. 9.

    OFIRMEV (acetaminophen) injection prescribing information. San Diego, CA: Cadence Pharmaceuticals, Inc.; 2010.

  10. 10.

    Prince JS, Dungy D. When IV acetaminophen costs skyrocketed, one health system did some new math. Drug Topics. Available at: (last accessed December 27, 2019)

  11. 11.

    Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse effects after major surgery in intensive care unit. J Crit Care. 2010;25(3):458–62.

    CAS  Article  Google Scholar 

  12. 12.

    Duggan ST, Scott LJ. Intravenous paracetamol (acetaminophen). Drugs. 2009;69:101–13.

    CAS  Article  Google Scholar 

  13. 13.

    Jahr JS, Lee VK. Intravenous Acetaminophen. Anesthesiol Clin. 2010;28:619–45.

    CAS  Article  Google Scholar 

  14. 14.

    Bannwarth B, Péhourcq F. Pharmacologic basis for using paracetamol: pharmacokinetic and pharmacodynamic issues. Drugs. 2003;63:5–13.

    CAS  Article  Google Scholar 

  15. 15.

    Mitra S, Arora J, Ahuja V, Takkar N. Combined spinal-epidural for labour analgesia with low-dose bupivacaine but without any opioid in the spinal component: can we improve upon the traditional? Acta Anaesthesiol Belg. 2015;66:9–15.

    CAS  PubMed  Google Scholar 

  16. 16.

    Mardirosoff C, Dumont L, Boulvain M, Tramer MR. Foetal bradycardia due to intrathecal opioids for labour analgesia: a systematic review. Br J Obstet Gynaecol. 2002;109:274–81.

    Article  Google Scholar 

  17. 17.

    Elbohoty AE, Abd-Elrazek H, Abd-El-Gawad M, Salama F, El-Shorbagy M, Abd-El-Maeboud KH. Intravenous infusion of paracetamol versus intravenous pethidine as an intrapartum analgesic in the first stage of labor. Int J Gynaecol Obstet. 2012;118:7–10.

    CAS  Article  Google Scholar 

  18. 18.

    Abd-El-Maeboud KH, Elbohoty AE, Mohammed WE, Elgamel HM, Ali WA. Intravenous infusion of paracetamol for intrapartum analgesia. J Obstet Gynaecol Res. 2014;40:2152–7.

    CAS  Article  Google Scholar 

  19. 19.

    Abdollahi MH, Mojibian M, Pishgahi A, Mallah F, Dareshiri S, Mohammadi S, et al. Intravenous paracetamol versus intramuscular pethidine in relief of labour pain in primigravid women. Niger Med J 2014; 55: 54–7.

  20. 20.

    Lallar M, Anam H, Nandal R, Singh SP, Katyal S. Intravenous paracetamol infusion versus intramuscular tramadol as an intrapartum labour analgesic. J Obstet Gynecol India. 2015;65:17–22.

    CAS  Article  Google Scholar 

  21. 21.

    Kaur Makkar J, Jain K, Bhatia N, Jain V, Mal MS. Comparison of analgesic efficacy of paracetamol and tramadol for pain relief in active labor. J Clin Anesth. 2015;27:159–63.

    CAS  Article  Google Scholar 

  22. 22.

    Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2016;75(3):552-9

  23. 23.

    Martingano D, Hood K, Mersch M, Cuadra G, Nuamah J, Rawson A, et al. Concurrent use of prostaglandin E2 and acetaminophen is associated with longer duration of labor induction. Am J Obstet Gynecol 2021;S616

  24. 24.

    Simmons SW, Cyna AM, Dennis AT, Hughes D. Combined spinal-epidural versus epidural analgesia in labour. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003401.

  25. 25.

    Wang Q, Zheng SX, Ni YF, Lu YY, Zhang B, Lian QQ, Hu MP. The effect of labor epidural analgesia on maternal-fetal outcomes: a retrospective cohort study. Arch Gynecol Obstet. 2018;298:89–96.

    Article  Google Scholar 

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RP: patient recruitment, data acquisition, conduct of the study, writing the project report, writing up the first draft of the paper. SM: conception and design of the study, statistical analysis and interpretation of data, revising the draft paper critically for important intellectual content. JS: analysis and interpretation of data, revising the draft paper critically for important intellectual content. RaS: analysis and interpretation of data, revising the draft paper critically for important intellectual content. BG: patient recruitment and data acquisition, revising the draft paper critically for important intellectual content.

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Correspondence to Sukanya Mitra.

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Panghal, R., Mitra, S., Singh, J. et al. Oral acetaminophen as an adjunct to continuous epidural infusion and patient-controlled epidural analgesia in laboring parturients: a randomized controlled trial. J Anesth (2021).

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  • Acetaminophen
  • Oral
  • Adjunct
  • Labor analgesia
  • Combined spinal–epidural
  • Patient-controlled epidural analgesia